High density lipoproteins (HDL) circulate in the blood of vertebrates, transporting cholesterol from various body tissues to the liver for excretion or recycling. HDL particles are protein-lipid complexes of apolipoprotein A-I (apoA-I), several minor proteins, phospolipids, cholesterol, and cholesterol esters. Reconstituted HDL (rHDL), developed in the Jonas lab, have provided the best opportunities to experimentally study the structure-function relationships of apoA-I because of their defined compositions and sizes [76]. Nascent rHDL particles consist of a phospolipid bilayer disk surrounded by two apoA-I molecules. The amphipathic helices of apoA-I shield the hydrophobic lipid tails, solubilizing the rHDL particle in water. The Harvey group has used NAMD and VMD to carry out and analyze molecular dynamics simulations on a model HDL particle consisting of twenty POPC lipids and twelve synthetic alpha-helical 18-mer peptides with an apolipoprotein-like charge distribution immersed in an appropriate solvent bath [77]. This simulation of 28,552 atoms covered approximately one nanosecond of total time and required several months of CPU time on the Resource computers. Several possible salt bridges between and within helices were studied. Some salt bridges appeared to be stable based on estimated values of ?G for salt bridge formation. The structure of rHDL has not been observed experimentally as protein-lipid complexes are extremely difficult to crystallize. Hence, Resource personnel have constructed a model of the lipid-binding domain of apoA-I in rHDL particles* based on experimental evidence and sequence analysis [78]. The total system, comprising two apolipoproteins, 160 POPC lipids, and 6,224 water molecules, 46,522 atoms in all, was tested via simulated annealing using NAMD 2 for a total of 250 ps. Future work will focus on improving this current picket-fence model of HDL, as well as incorporating information from a recent lipid-free crystal structure of the apoA-I lipid-binding domain which exhibits in a lipid-free complex of four proteins an alternative belt-like structure [79].